title: Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk: a meta-analysis.
abstract: BACKGROUND
  Polymorphisms in the cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene have been implicated in susceptibility to cancer, but the many published studies have reported inconclusive results. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of cancer.
  
  
  METHODS
  The PubMed and EMBASE databases were searched for all articles published up to September 19, 2010 that addressed cancer and polymorphisms, variants, or mutations of CTLA-4. A statistical analysis was performed using proprietary statistical software.
  
  
  RESULTS
  Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 48 case-control studies from 27 articles were analyzed. The results indicated that individuals who carried the +49 G allele (AG + GG) had a 16% decreased risk of cancer compared with homozygotes (+49AA; odds ratio [OR], 0.84; 95% confidence interval [CI], 0.74-0.95). However, there was no significant association between the risk of cancer and the -318C/T polymorphism or the CT60 polymorphism (-318C/T: OR, 1.23; 95% CI, 0.99-1.54 for TT + TC vs CC; CT60: OR, 1.02; 95% CI, 0.80-1.29 for AA + AG vs GG). In further stratified analyses for the +49A/G and -318C/T polymorphisms, the decreased risk of cancer remained in subgroups of Europeans, patients with breast cancer, and patients with lung cancer for the +49A/G polymorphism; whereas an increased risk of cancer was observed among Europeans for the -318C/T polymorphism.
  
  
  CONCLUSIONS
  Results from the current meta-analysis suggested that the +49A/G and -318C/T polymorphisms in CTLA-4 are risk factors for cancer. To further evaluate gene-gene and gene-environment interactions between CTLA-4 polymorphisms and the risk of cancer, more studies with larger groups of patients will be required.
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.forename: Can
authors.initials: C
authors.lastname: Tian
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human